An interesting tumor associated antigen which could be used as target in antibody therapy is the CD146 antigen.
CD146 (cluster of differentiation 146) also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, is a 113 kDa cell adhesion molecule currently used as a marker for endothelial cell lineage. In humans, the CD146 protein is encoded by the MCAM gene.
Upregulation of this antigen was first described for malignant cells of melanocytic lineage (Lehmann et al., 1987) and later it was found to be a marker of disease progression in malignant melanoma (Lehmann, et al., 1989). The expression of this antigen was found to be up-regulated in several cancer forms, including melanoma, prostate cancer, breast cancer, mesothelioma, pancreatic carcinoma, osteosarcoma and lung cancer (Sers et al., 1994; Filshie, et al., 1998; Wu et al., 1998; Kristiansen et al., 2003; McGary et al, 2003; Aldovini et al., 2006; Bidlingmaier et al, 2009). It is also observed in association with inflammation (Middleton et al 2005; Bardin et al., 2006). In normal mature tissues, expression of CD146 is found on endothelial cells, smooth muscle cells, a subpopulation of activated T-lymphocytes and intermediate trophoblasts (Pickl et al., 1997; Shih et al., 1996; Sers et al., 1994). Thus CD146 could be a target for cancer therapy.
The use of monoclonal antibodies has increased steadily since its discovery in the 1970s and today it is a multi-billion industry. Antibody based treatments have been developed against a number of cancer associated antigens including Her-2 and CD20 and today monoclonal antibodies constitutes an important class of therapeutics.
The mechanisms of action of monoclonal antibodies in targeted therapy are diverse. Some therapeutic antibodies act by arresting proliferation of target cell by binding to the target antigen receptor on the cell surface. Other monoclonal antibodies have been developed (chimeric, humanized, fully human) to interact with human immune effectors (e.g. complement factors, Natural Killer cells) to stimulate targeted tumor cell kill by these immune effectors. Monoclonal antibodies can be further developed as targeting entities by conjugation to nanoparticles or microparticles made from polymers or proteins or inorganic crystals or a combination thereof, carrying cytotoxic drugs or radioactive molecules. The monoclonal antibodies can also be directly conjugated to drugs (Antibody Drug Conjugates) (Sinha et al., 2006, Peer et al., 2007, Sievers &.Senter, 2013)
Monoclonal antibodies have been developed against the CD146 antigen in the past and in vitro and in vivo testing of targeting with anti-CD146 monoclonal antibodies has shown a considerable promise (McGary et al., 2003; Melnikova et al., 2006; Ma et al., 2010). Although the function of CD146 is not fully understood, proliferative function has been shown to be inhibited by antibody binding, and CD146 has been described as a new co-receptor for VEGFR-2 and a promising target for blocking tumor-related angiogenesis (Jiang et al., 2012). CD146 has also been studied as a potential antigen for targeted-internalizing immunoliposome-technology (Iyer et al, 2011).